Changes in Cyclic Guanosine Monophosphate Channel of 661w Cells In vitro with Excessive Light Time

Purpose: To determine the response time and protective mechanism of the cyclic guanosine monophosphate (cGMP) channel in 661w cells. Methods: 661w cells were exposed to 4500Lux visible light for three and four days at the following exposure time periods per day: 20, 30, 60, 90, 120, and 180. Cells were incubated for the rest of the time without any other treatment. Cell activity and cell death rates were measured with Hoechst/PI (diphenylmethane/propidium iodide) staining. Western Blot was used to detect the levels of guanylate cyclase-activating proteins 1 (GCAP1), cGMP, and phosphodiesterase (PDE)6 in the cGMP-gated channel. Results: 661w cells showed low mortality within three days. The mortality rate increased from the fourth day, especially during the longer times (120 and 180 min) of light exposure. After three-day illumination, the level of cGMP increased after 20 and 90 min and the level of GCAP1 increased after 60 and 90 min. After four days of illumination, the level of GCAP1 upregulated after a time of 20 and 60 min, while the cGMP level decreased from 30 min. The expression of PDE6 upregulated at each light period. Conclusion: The survival rate of 661w cells was relevant to the time of light exposure. The changes in GCAP1, cGMP, and PDE6 levels over time were possibly related to cell metabolism and restoration after light-induced damage

Continual Named Entity Recognition without Catastrophic Forgetting

Continual Named Entity Recognition (CNER) is a burgeoning area, which involves updating an existing model by incorporating new entity types sequentially. Nevertheless, continual learning approaches are often severely afflicted by catastrophic forgetting. This issue is intensified in CNER due to the consolidation of old entity types from previous steps into the non-entity type at each step, leading to what is known as the semantic shift problem of the non-entity type. In this paper, we introduce a pooled feature distillation loss that skillfully navigates the trade-off between retaining knowledge of old entity types and acquiring new ones, thereby more effectively mitigating the problem of catastrophic forgetting. Additionally, we develop a confidence-based pseudo-labeling for the non-entity type, \emph{i.e.,} predicting entity types using the old model to handle the semantic shift of the non-entity type. Following the pseudo-labeling process, we suggest an adaptive re-weighting type-balanced learning strategy to handle the issue of biased type distribution. We carried out comprehensive experiments on ten CNER settings using three different datasets. The results illustrate that our method significantly outperforms prior state-of-the-art approaches, registering an average improvement of $6.3$\% and $8.0$\% in Micro and Macro F1 scores, respectively.Comment: Accepted by EMNLP2023 main conference as a long pape

Motorized Photomodulator:Making A Non-photoresponsive Supramolecular Gel Switchable by Light

Introducing photo-responsive molecules offers an attractive approach for remote and selective control and dynamic manipulation of material properties. However, it remains highly challenging how to use a minimal amount of photo-responsive units to optically modulate materials that are inherently inert to light irradiation. Here we show that the application of a light-driven rotary molecular motor as a "motorized photo-modulator" to endow a typical H-bond-based gel system with the ability to respond to light irradiation creating a reversible sol-gel transition. The key molecular design feature is the introduction of a minimal amount (1 mol%) of molecular motor into the supramolecular network as a photo-switchable non-covalent crosslinker. Advantage is taken of the subtle interplay of the large geometry change during photo-isomerization of the molecular motor guest and the dynamic nature of a supramolecular gel host system. As a result, a tiny amount of molecular motors is enough to switch the mechanical modulus of the entire supramolecular systems. This study proves the concept of designing photo-responsive materials with minimum use of non-covalent light-absorbing units.</p

Research progress of MDSCs-targeted immunotherapy for pancreatic cancer

Pancreatic cancer (PC) is a highly malignant digestive system tumor with a poor survival rate and prognosis. Most patients with pancreatic cancer have no obvious clinical manifestations in the early stage of the disease, and are found to be in the middle and late stage of the disease when they seek treatment.A unique and complex tumor microenvironment (TME) is formed during its development and evolution. Due to the occult nature of pancreatic cancer, for patients with advanced pancreatic cancer, some traditional treatment methods such as surgical resection and chemotherapy are very limited, and there is a lack of effective treatment programs. Of course, this is also related to the immunosuppression of the TME of pancreatic cancer. Some immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), play an important immunosuppressive role in helping tumor immune escape. Therefore, it is considered to be a major difficulty in the treatment of pancreatic cancer. In recent years, with the in-depth study of TME, immunotherapy has gradually become a new therapeutic strategy, and has made great progress in the treatment of various malignant tumors. The study found that targeted MDSCs therapy is a new and effective treatment for pancreatic cancer.In this paper, we introduce the role of MDSCs in TME and their progress as potential targets for immunotherapy of pancreatic cancer, hoping to provide new directions for the treatment of pancreatic cancer and other tumors

USP6-associated soft tissue tumors with bone metaplasia: Clinicopathologic and genetic analysis and the identification of novel USP6 fusion partners

IntroductionAmong those tumors with consistent USP6 rearrangement, some arise from soft tissue and show bone metaplasia, including myositis ossificans (MO), fibro-osseous pseudotumor of digits (FOPD), soft tissue aneurysmal bone cyst (ST-ABC) and fasciitis ossificans (FO). These lesions are easily confused with malignancies because they show a rapid growth rate and brisk mitoses. Here, we aim to clarify the clinicopathologic and genetic characteristics of this entity and analyze the correlations among the different subtypes in one of the largest cohorts.Materials and MethodsThe clinicopathologic features of 73 cases of MO, FOPD, ST-ABC and FO diagnosed at West China Hospital, Sichuan University from January 2010 to December 2021 were retrospectively analyzed. Forty-three undecalcified samples were analyzed by systematic genetic studies, including fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), Sanger sequencing and next-generation-based sequencing were performed.ResultsThis series included 40 males and 33 females aged 2 to 80 years old (median: 31 years). FOPD occurred in extremal soft tissue, while lower extremities (38/58, 65.5%) were the most commonly involved lesions in the other three subgroups. Histologically, proliferative myofibroblasts/fibroblasts with varying degrees of osteoid tissue were present. Fluorescence in situ hybridization (FISH) results indicated that 22 cases (22/27, 81.5%) were positive for USP6 rearrangement, and 5 cases were negative. Among those cases with positive FISH results, 18 underwent reverse transcription-polymerase chain reaction (RT-PCR) detection that successfully detected common USP6 fusion types. Thirteen cases showed COL1A1::USP6 fusion, one showed MYH9::USP6 fusion, and 4 were negative for common fusion types. Next-generation-based sequencing technology was performed on two lesions with negative RT–PCR results and novel fusion partners SNHG3 and UBE2G1 were discovered.ConclusionsOur findings revealed that COL1A1 is the most common fusion partner in this entity, unlike primary aneurysmal bone cysts and nodular fasciitis. Notably, we believed that FO may demonstrate more similar clinicopathologic and genetic manifestations with MO/FOPD and ST-ABC instead of nodular fasciitis for involving lower limbs most frequently and showing recurrent COL1A1::USP6 fusion. Additionally, this study also found two novel USP6 fusion partners, which further expanded our knowledge of this neoplastic spectrum

Design of novel inhibitors of trypanosomatid parasites

Neglected tropical diseases (NTDs) are a group of infectious diseases that are endemic in tropical and subtropical regions. The associated infectious agents include protozoa, bacteria, viruses, and helminth parasites. In particular, Human African Trypanosomiasis, Chagas disease and Leishmaniasis are responsible for high mortality and morbidity rates in developing countries. However, the current treatments for trypanosomiasis and leishmaniasis have severe side effects and can be lethal. Most of these treatments are antiquated, resulting in emerging drug resistance, and are difficult to administer (mostly by injection). Therefore, there is an urgent demand to find safer, cheaper, and more efficient alternatives to the existing drugs. Natural products play an important part in drug discovery, with more than 50 % of modern drugs being directly or indirectly derived from them. In particular, the natural product chamuvarinin was found to have potent activity against trypanosomatid parasites. In this project, we synthesized a series of chamuvarinin based analogues, aiming to expand the library of trypanosomatid inhibitors, and further exploring the structure-activity relationship (SAR)

A Comparative Study on the Cultural Dimensions and Health Perception of the COVID-19 Pandemic between China and the United States

When a public crisis such as COVID-19 occurs, factors that affect health-related behaviors, such as compliance with safety precautions, health professionals, and directives from government agencies will become more obvious. This research explores the differences between the people of the United States and China regarding preventive behavioral intentions, perceptions of personal and social risks, seriousness, and other cultural characteristics in the context of the COVID-19 health crisis. The purpose is to provide insights that can be used when global public health events occur in the future. A total of 536 people who lived in the US and China from 12 July to 7 September 2020 were recruited in the survey. Through a web-based survey, differences in the attitudes and perceptions of COVID-19 between the two countries were identified. Overall, the people of China scored higher than Americans on several measures regarding personal risk perception, social risk perception, and seriousness. Chinese citizens also had higher preventive behavioral intentions than their US counterparts. In addition, the relationships between cultural dimensions and health-related variables were also different

Point Cloud Information Extraction for Streetlights with Vehicle-borne LiDAR

The acquisition of detailed information for the streetlights in a large scene remains a tough task since the streetlights are of great number and types. In this paper, a method is proposed to extract and classify the streetlights, with the aid of prior sample sets on the basis of skeleton-line-buffer discriminant algorithm. First, a model and a priori sample set for streetlights are established according to the expression characteristics of streetlights in vehicle-borne LiDAR point cloud. Secondly, with the theory and method of mathematical morphology, the rod-shaped objects are extracted in vehicle LiDAR point cloud scene, and the candidate streetlights are chosen under the constraint of streetlight model and semantic rules. Then, the candidate samples are selected from the sample sets according to the parameter information and the statistical information obtained from the selected streetlights. Finally, based on the matching algorithm of least squares theory, we select and match the priori samples of streetlights and the candidate streetlights. Based on the double buffer of streetlight skeleton information, we discriminate and analyze the candidate streetlights to achieve the extraction and identification of street lights. Finally, the priori samples of streetlights and the point cloud of the candidate streetlights are matched and screened with the matching algorithm of least square theory; and based on the double buffer of streetlight skeleton information, the candidate streetlights are discriminated and analyzed to achieve the extraction and identification of streetlights. Our experiment shows that the algorithm is efficient and robust for the extraction of detailed information of streetlights. For the streetlights with less occlusion and relatively complete data, the extraction accuracy is 0.952, and for those with serous occlusion, low point cloud density and poor data integrity, the extraction accuracy is 0.780. And the above results validate the robustness of the proposed algorithm for the extraction of intermediate streetlights from large scenes. The detailed information extracted by the algorithm can be used to serve the fine and dynamic management of streetlights in large scenes

Synthesis of 2,4,6,8,10-pentaaza[3.3.3]propellane substituted with different groups

Polyaza[3.3.3]propellanes have good symmetry and strong ring tension, which are suitable as the skeleton structure of functional materials such as high energy density materials. Based on the single benzyl derivative of 3,7,9.11-tetraoxo-2,4,6,8,10-pentaaza[3.3.3]propellane (compound 3 ), a series of 2,4,6,8,10- pentaaza[3.3.3]propellane derivatives, such as 4a-c and their reduced derivatives 5a-c, were synthesized successfully

Biochemical and microstructural determinants of the development of serous retinal detachment secondary to retinal vein occlusion

Purpose: To study the alteration of cytokine factors in aqueous humor and retinal microstructure in the formation of serous retinal detachment (SRD) secondary to retinal vein occlusion. Methods: The subjects were 39 patients with RVO, of whom 31 patients had SRD (RVO-SRD). Spectral Domain Optical Coherence Tomography (SD-OCT) was used to measure the completeness of photoreceptor inner segment/outer segment (IS/OS) and the external limiting membrane (ELM) as well as the structure of RVO-SRD, including the height and shape of SRD. The aqueous humor was collected before intravitreal injection of Ranibizumab. The concentrations of VEGF, MCP-1, IL-8, IL-6, b-FGF and TNF-α in the aqueous humor were measured. All patients participated in the 6-month follow-up examinations, which included visual acuity, intraocular pressure, ophthalmologic examination, and SD-OCT. The time of recurrence of RVO-SRD was recorded. Results: The formation of SRD was associated with the area of congested vein, disrupted IS/OS, ELM layers and high VEGF, MCP-1, IL-8, IL-6 levels. However, the height and shape of SRD were not relevant to any inflammatory factors. Moreover, high levels of MCP-1, IL-8 and IL-6 were found in large areas of congested veins. High levels of MCP-1 and IL-6 were observed in the patients with incomplete IS/OS and ELM. The recurrence of SRD was related to the high MCP-1 level. Conclusion: High concentrations of cytokine factors in aqueous humor could induce vascular leakage, exacerbate the extent of macular edema, disrupt the structure of ELM and IS/OS, and develop SRD in RVO